RESUMEN
We predicted vigabatrin dosages for adjunctive therapy for pediatric patients with refractory complex partial seizures (rCPS) that would produce efficacy comparable to that observed for approved adult dosages. A dose-response model related seizure-count data to vigabatrin dosage to identify dosages for pediatric rCPS patients. Seizure-count data were obtained from three pediatric and two adult rCPS clinical trials. Dosages were predicted for oral solution and tablet formulations. Predicted oral solution dosages to achieve efficacy comparable to that of a 1 g/day adult dosage were 350 and 450 mg/day for patients with body weight ranges 10-15 and >15-20 kg, respectively. Predicted oral solution dosages for efficacy comparable to a 3 g/day adult dosage were 1,050 and 1,300 mg/day for weight ranges 10-15 and >15-20 kg, respectively. Predicted tablet dosage for efficacy comparable to a 1 g/day adult dosage was 500 mg/day for weight ranges 25-60 kg. Predicted tablet dosage for efficacy comparable to a 3 g/day adult dosage was 2,000 mg for weight ranges 25-60 kg. Vigabatrin dosages were identified for pediatric rCPS patients with body weights ≥10 kg.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia Parcial Compleja/tratamiento farmacológico , Pediatría , Vigabatrin/uso terapéutico , Adulto , Peso Corporal , Química Farmacéutica , Niño , Preescolar , Planificación en Salud Comunitaria , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lactante , MasculinoRESUMEN
AIMS: Glycemic control immediately after hospital admission is difficult. This study aimed to develop an algorithm-based approach to initiate insulin therapy on admission. METHODS: Patients with history of diabetes mellitus admitted at UC Davis medical center, with any blood glucose (BG) value ≥ 180 mg/dL, or who received any insulin within the first 24 h of hospitalization were selected for a retrospective chart review. RESULTS: Total of 315 patient records were studied. Patients prescribed insulin prior to admission had higher 24-hour average BG and higher corrected total daily dose of insulin (CxTDD), compared with the patients who were not prescribed insulin prior to admission. For the patients not receiving home insulin and not given new glucocorticoids, first BG upon presentation correlated with the risk of first 24-hour average BG > 180 mg/dL. Factors associated with CxTDD were first BG, weight, oral intake, and glucocorticoid dose. Home insulin daily dose, opiate/intravenous pain medication and systemic inflammatory response syndrome were associated with CxTDD only in the patients receiving home insulin. CONCLUSIONS: A subgroup of patients can be given correction insulin as a sole initial treatment on admission. For patients requiring basal-bolus insulin, several factors associated with the initial insulin requirements are identified.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Alcaloides Opiáceos , Glucemia , Glucocorticoides/uso terapéutico , Humanos , Hipoglucemiantes/efectos adversos , Insulina , Insulina Regular Humana/uso terapéutico , Alcaloides Opiáceos/uso terapéutico , Estudios RetrospectivosRESUMEN
Aims: Tacrolimus has extensive pharmacokinetic variability among patients and a narrow therapeutic window. The U.S. Clinical Pharmacogenetics Implementation Consortium recommends a starting dose for tacrolimus of 0.15-0.3 mg/kg/day, which is much higher compared with 0.05-0.15 mg/kg/day used in China. The purpose of this study was to investigate the influence of clinical factors and single nucleotide polymorphisms (SNPs) on tacrolimus concentrations in Chinese renal transplant recipients. Methods: This study enrolled 406 tacrolimus-treated patients. After renal transplantation, the first tacrolimus trough concentration and corresponding clinical information were collected from all patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to genotype 15 SNPs. The relationship between the genetic and clinical factors and dose-adjusted tacrolimus trough concentration was examined. The tacrolimus starting dose was predicted using a classification and regression tree analysis. Results: Examination of the 15 SNPs and several clinical factors identified the CYP3A5 genotype (p = 5.6 × 10-11) and hemoglobin (p = 8.4 × 10-10) as the most significant determinants of tacrolimus C0/D. Accordingly, a concise tacrolimus recommendation dosage model, a classification scheme, and a regression tree were developed. Conclusion: A new classification and regression tree model was developed for establishing the starting dose of tacrolimus based on the CYP3A5 genotype and hemoglobin values. This result may help clinicians prescribe an appropriate initial tacrolimus dose. ClinicalTrials.gov ID: 2020-KY-147.
Asunto(s)
Citocromo P-450 CYP3A/genética , Hemoglobinas/genética , Tacrolimus/administración & dosificación , Adulto , Alelos , Pueblo Asiatico , Biomarcadores Farmacológicos , China , Citocromo P-450 CYP3A/metabolismo , Femenino , Genotipo , Humanos , Inmunosupresores/administración & dosificación , Riñón/patología , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Farmacogenética/métodos , Polimorfismo de Nucleótido Simple/genética , Tacrolimus/farmacocinética , Tacrolimus/uso terapéuticoRESUMEN
PURPOSE: Liver transplantation is the treatment of choice for patients with end-stage liver disease. Due to the between- and within-individual pharmacokinetic variability in tacrolimus, used to prevent rejection after transplantation, it is difficult to predict the dose needed achieve the target levels in the blood. This study aimed to construct a population pharmacokinetic model of tacrolimus dosage prediction for therapeutic drug monitoring in clinical settings for Korean adult patients receiving living donor liver transplantation (LDLT). METHODS: A total of 58 Korean adult patients receiving LDLT with tacrolimus administration were enrolled. Demographic, clinical, and CYP3A5*1/*3 polymorphism data were collected. Population pharmacokinetic modeling of tacrolimus during the first 14 days after transplantation was performed using NONMEM program. Parameters were estimated by the first-order conditional estimation with interaction method. The internal validation of the final model was assessed by the bootstrap and visual predictive check methods using 500 samples from the original data. RESULTS: One-compartmental model was selected as a base model. After the stepwise covariate model building process, postoperative day (POD) and combinational CYP3A5 genotype of the recipient and donor were incorporated into clearance (CL/F). The estimated typical values of CL/F and volume of distribution (V/F) were 6.33 L/h and 465 L, respectively. The final model was CL/F =6.33× POD0.257×2.314 (if CYP3A5 expresser recipient grafted from CYP3A5 expresser donor) ×1.523 (if CYP3A5 expresser recipient grafted from CYP3A5 nonexpresser donor) and V/F =465× POD0.322. CONCLUSION: A population pharmacokinetic model for tacrolimus was established successfully in Korean adult patients receiving LDLT. This model is expected to contribute to improving patient outcomes by optimizing tacrolimus dose adjustment for liver transplant patients.